Assessment of VEGF and TNF-alpha levels in patients with an unexpectedly poor and suboptimal response during the treatment of infertility using ART methods

Q3 Pharmacology, Toxicology and Pharmaceutics
V. N. Perfilova, E. A. Muzyko, K. Y. Tikhaeva, M. V. Kustova, Anna V. Mukhina, Anna Yu. Fokina, Evgeniya I. Zhuravleva, Tatyana D. Lenskaya
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Abstract

Introduction: The problem of infertility treatment currently has medical, socio-demographic and economic significance. Progress in the field of reproductive technologies has improved the situation, but the issue has not yet been completely resolved. Infertility is diagnosed in 8-12% of couples of reproductive age; in Russia this figure exceeds 15%, and, according to WHO, it is a critical level. It is known that immunological factors can disrupt the reproductive process at the stages of folliculogenesis, ovulation, and implantation. These include vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and others. The aim of this study: to assess the levels of VEGF and TNF-α in women with different outcomes of hormonal stimulation of the ovaries during the treatment of infertility using ART methods. Materials and methods: Based on voluntary informed consent, a simple open comparative randomized study was conducted with the participation of 71 women in the Volgograd region undergoing infertility treatment using ART methods. Inclusion criteria were the age up to 42 years inclusive and the anti-Mullerian hormone level over 1.2 ng/mL. Before ovulation stimulation with gonadotropins, data on ovarian reserve parameters were collected. Based on the results of stimulation, women were divided into 3 groups: Group 1 – with high and normal ovarian response – 10 or more oocytes were obtained (control group); Group 2 – with suboptimal ovarian response – 5-9 oocytes received; Group 3 – with a poor response – 4 or less oocytes were received. After venipuncture, which was performed in preparation for standard anesthesia, VEGF and TNF-α were quantitatively determined in the blood plasma using an enzyme-linked immunosorbent assay. Results: The study results showed a statistically significant difference in VEGF levels in follicular fluid and serum between the groups of women with high/normal, suboptimal and poor ovarian response to gonadotropin stimulation. A higher level of this marker was observed in the serum of patients with high/normal and poor response – 48.15±4.23 and 41.29±8.26 pg/mL, respectively, while in women with a suboptimal response a lower VEGF level was determined –29.19±3.41 pg/mL. The levels of VEGF in the follicular fluid of women included in the high/normal, suboptimal and poor response groups were 35.95±3.20; 27.42±2.53 and 41.22±3.23 pg/mL, respectively (Table 1). As for TNF-α, its serum level in women with a high and normal response was lower than in the patients with a suboptimal response. In the follicular fluid of patients of group 3, there was a higher level of TNF-α, compared to groups 1 and 2, where the indicator was almost the same. However, the difference was not statistically significant. Conclusions: Thus, VEGF is directly involved in the mechanisms of regulation of oocyte maturation and can be not only a marker of poor ovarian response, but also a predictor of unsatisfactory results of ovarian stimulation in the treatment of infertility using ART methods. TNF-alpha in follicular fluid does not have a statistically significant effect on follicle development in the treatment of infertility using assisted reproductive technologies.
评估使用抗逆转录病毒疗法治疗不孕症期间意外反应不佳和不理想患者的血管内皮生长因子和 TNF-α 水平
导言目前,不孕症治疗问题在医学、社会人口和经济方面都具有重要意义。生殖技术领域的进步改善了这一状况,但这一问题尚未完全解决。8%-12%的育龄夫妇被诊断出患有不孕症;在俄罗斯,这一数字超过了 15%,世界卫生组织认为这是一个临界水平。众所周知,免疫因素会在卵泡生成、排卵和着床阶段干扰生殖过程。这些因素包括血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)等。本研究的目的是:在使用 ART 方法治疗不孕症期间,评估不同激素刺激卵巢结果的妇女体内血管内皮生长因子和 TNF-α 的水平:在自愿知情同意的基础上,对伏尔加格勒地区 71 名接受抗逆转录病毒疗法治疗的不孕症妇女进行了简单的开放式随机比较研究。纳入标准为年龄不超过 42 岁(含 42 岁),抗穆勒氏管激素水平超过 1.2 纳克/毫升。在使用促性腺激素刺激排卵前,收集了卵巢储备参数数据。根据刺激结果,妇女被分为 3 组:第 1 组--卵巢反应高且正常--获得 10 个或更多卵细胞(对照组);第 2 组--卵巢反应欠佳--获得 5-9 个卵细胞;第 3 组--反应欠佳--获得 4 个或更少卵细胞。在准备标准麻醉的情况下进行静脉穿刺后,使用酶联免疫吸附试验定量测定血浆中的 VEGF 和 TNF-α:研究结果显示,卵泡液和血清中的 VEGF 水平在促性腺激素刺激下卵巢反应高/正常组、卵巢反应不佳组和卵巢反应差组之间存在显著统计学差异。在卵巢反应高/正常和反应差的患者血清中,该标记物的水平较高,分别为(48.15±4.23)和(41.29±8.26)pg/mL,而在反应次佳的妇女中,VEGF 水平较低(29.19±3.41)pg/mL。高/正常组、次优组和不良反应组妇女卵泡液中的VEGF水平分别为(35.95±3.20)、(27.42±2.53)和(41.22±3.23)pg/mL(表1)。至于 TNF-α,高反应和正常反应妇女的血清水平低于反应不佳的患者。在第 3 组患者的卵泡液中,TNF-α 的水平较高,而在第 1 组和第 2 组中,该指标几乎相同。然而,差异并无统计学意义:因此,血管内皮生长因子直接参与卵母细胞成熟的调节机制,它不仅可以作为卵巢反应不良的标志物,还可以作为使用 ART 方法治疗不孕症时卵巢刺激效果不理想的预测因子。在使用辅助生殖技术治疗不孕症的过程中,卵泡液中的α-TNF对卵泡发育没有统计学意义上的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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